The use of coenzyme Q10 in congestive heart failure continues to be advocated on the basis of anecdotal information and uncontrolled data. Dr. Sinatra's letter uses unsubstantiated theoretical concerns to ignore and discount the implications of a negative controlled trial. It is possible that higher concentrations of a substance might be more beneficial than lower concentrations. Nevertheless, in patients with heart failure, most drugs that are useful at high doses are also effective at lower doses. To use Dr. Sinatra's example, patients receiving angiotensin-converting enzyme inhibitors have fewer hospitalizations when the drug is given at a high dose, but these drugs are clearly of benefit with lower doses (1). Similarly, β-blockers are effective at low doses, although higher doses appear more beneficial (2). If coenzyme Q10 blood concentrations of 2.9 µg/mL are truly optimal, concentrations that are slightly lower but more than double the baseline level (as realized and documented in our study) should still be effective. No published data indicate that the coenzyme Q10 concentrations needed for patients with heart failure are higher than those achieved in our study. As discussed in our article, studies advocating coenzyme Q10 for heart failure have used doses lower than those we administered. Furthermore, mean serum concentrations more than doubled in our study to 2.2 µg/mL, higher than the concentration achieved in the study (3) quoted by Dr. Sinatra. The authors of that study concluded that concentrations of 2.5 µg/mL are optimal, but they provided no data to support this conclusion. Other experiences quoted by Dr. Sinatra are also anecdotal.